The long term goal of the proposed research is increased understanding of certain aspects of fibrinogen biosynthesis, the carbohydrate content (sialic acid) of fibrinogen and its relationship to synthesis. Studies are designed to increase understanding of the basic mechanisms involved in the regulation of fibrinogen synthesis by parenchymal cells of the liver. Particular attention will be directed at the mechanism by which the plasma degradative fibrinogen fragments D and E increase the synthesis of fibrinogen in the intact rabbit. To directly answer this question, the hepatic parenchymal cells will be isolated and studied in a controlled environment, in vitro. Of particular interest is the observation that fibrinogen fragments D and E stimulate fibrinogen synthesis, while the same fragments from fibrin do not. Studies have been designed to determine whether the polypeptide or carbohydrate portion of fragments D and E are responsible for their stimulatory capacity. These studies will provide further understanding of fibrinogen biosynthesis and the clottability of this protein.